Synthesis of miltirone analogues as inhibitors of Cdc25 phosphatases

• Published in: Bioorganic & medicinal chemistry letters Vol. 16; no. 7; pp. 1905 - 1908
• Main Authors: Huang, Weigang, Li, Jingya, Zhang, Wei, Zhou, Yueyang, Xie, Chuanming, Luo, Yu, Li, Yunfei, Wang, Jingli, Li, Jia, Lu, Wei
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.04.2006; Elsevier
• Subjects: Antineoplastic agents; Biological and medical sciences; Cancer; Cdc25 phosphatases; cdc25 Phosphatases - antagonists & inhibitors; Cell Line, Tumor; Drug Screening Assays, Antitumor; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; General aspects; Humans; Medical sciences; Miltirone; Pharmacology. Drug treatments; Phenanthrenes - chemical synthesis; Phenanthrenes - chemistry; Phenanthrenes - pharmacology; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases - antagonists & inhibitors; Miltirone; Cdc25 phosphatases; Cancer; Antineoplastic agent; Solid tumor; Phosphoprotein phosphatase; Lung; Phosphoric monoester hydrolases; Cytotoxicity; Esterases; Selectivity; Signal transduction; Structure activity relation; Colon; Chemical synthesis; Tumor cell; Human; Phenanthrene derivatives; Enzyme; Quinone; Enzyme inhibitor; Malignant tumor; In vitro; Cell line; Hydrolases
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.12.080

Miltirone analogues were synthesized and evaluated for inhibitory activity against Cdc25 and PTP1B. Most of the compounds demonstrated potent Cdc25 inhibitory activity, and several exhibited higher selectivity for Cdc25 than for PTP1B. In a cytotoxic assay, most of the compounds displayed cytotoxicity against the tumor cell lines A549 and HCT-116, producing IC 50 values in the micromolar range.